The in Vivo and in Vitro Effects of Exogenous Leptin on Ovulation in the Rat

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Abstract
Leptin, a hormonal product of the Lep gene, is expressed by adi- pocytes and is thought to play a role in regulating food intake and reproduction. The leptin protein has been localized in many repro- ductive tissues, including the ovary. Several publications indicate that the ovary is directly affected by leptin and that leptin may be a factor linking obesity and reproductive dysfunction. In this study, the effect of systemic leptin administration on ovulation in the rat ovary, both in vivo and in vitro, was investigated. Ip administration of leptin (30 mg at 3 hourly intervals for 15 h) to immature gonadotropin- primed rats caused a decline in ovulation in vivo, from 15.9 6 2.0 oocytes in the control animals to 5.3 6 1.6 oocytes in the leptin-treated animals (P , 0.001). Plasma progesterone and estradiol levels were analyzed immediately before ovulation, and neither was altered sig- nificantly in animals receiving the leptin treatment. Food consump- tion and body weight decreased following leptin treatment; however, a loss in body weight alone (pair-fed controls) was insufficient to explain the decrease in ovulation observed in the leptin-treated an- imals. In vitro perfusion of FSH-primed whole ovaries showed that treatment with leptin in combination with LH significantly decreased ovulations from 5.7 6 1.6 per ovary perfused with LH alone to 1.3 6 0.6 in those with LH and 1 mg/ml leptin (P , 0.05). Progesterone and estradiol levels in the samples taken during the perfusion period were unaffected by leptin treatment. In summary, leptin administration resulted in fewer ovulations, both in vivo and in vitro, but did not influence steroid levels. Systemic leptin administration at these doses can therefore inhibit ovulation, a process that occurs through a direct effect on the ovary. (Endocrinology 141: 1971-1976, 2000)

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